Dna sequencing using mosfet transistors

ABSTRACT

Embodiments of the invention include a method for fabricating a semiconductor device, the resulting structure, and a method for using the resulting structure. A substrate is provided. A hard mask layer is patterned over at least a portion of the substrate. Regions of the substrate not protected by the hard mask are doped to form a source region and a drain region. The hard mask layer is removed. A dielectric layer is deposited on the substrate. An insulative layer is deposited on the dielectric layer. A nano-channel is created by etching a portion of the insulative layer which passes over the source region and the drain region.

BACKGROUND OF THE INVENTION

The present invention relates generally to the field of transistors, andmore particularly to the use of metal-oxide-semiconductor field-effecttransistor (MOSFET) transistors for sequencing deoxyribonucleic acid(DNA).

Since the onset of the human genome project in 1990, many differentmethods of sequencing DNA have been developed in the interest ofreducing cost, required time, and sample volume while increasingaccuracy. Common DNA sequencing technologies in use today includesequencing by synthesis (SBS) methods where the DNA nucleotide sequenceis determined by the cyclic addition of nucleotide bases one base typeat a time using either natural nucleotides or fluorescently-labelednucleotides with a reversible terminator. Using these sequencingmethods, sequence read length is very limited and accuracy is typicallylow. Traditionally, strategies such as parallelization andminiaturization are utilized to improve the reliability and read speedof SBS sequencing methods while reducing the associated cost.

The use of DNA sequencing technology for quickly, reliably, andinexpensively sequencing the genome of mammals such as human beingsrequires further advancements in the field and the development of newsequencing methodologies.

SUMMARY

Embodiments of the invention disclose a method of fabricating asemiconductor device, a sensor, and a method of sequencing DNA. Asubstrate is provided. A hard mask layer is patterned over at least aportion of the substrate. Regions of the substrate not protected by thehard mask are doped to form a source region and a drain region. The hardmask layer is removed. A dielectric layer is deposited on the substrate.An insulative layer is deposited on the dielectric layer. A nano-channelis created by etching a portion of the insulative layer which passesover the source region and the drain region.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A depicts a top view of a semiconductor substrate and buried oxidelayer on which a MOSFET device for sequencing DNA may be fabricated, inaccordance with an embodiment of the invention.

FIG. 1B depicts a section view of a semiconductor substrate and buriedoxide layer on which a MOSFET device for sequencing DNA may befabricated, in accordance with an embodiment of the invention.

FIG. 2A depicts a top view of deposition and etching of a hard masklayer deposited on the semiconductor substrate of FIG. 1A, in accordancewith an embodiment of the invention.

FIG. 2B depicts a section view of deposition and etching of a hard masklayer deposited on the semiconductor substrate of FIG. 1A, in accordancewith an embodiment of the invention.

FIG. 3A depicts a top view of doped regions of the semiconductorsubstrate which form source and drain terminals of a MOSFET transistor,in accordance with an embodiment of the invention.

FIG. 3B depicts a section view of doped regions of the semiconductorsubstrate which form source and drain terminals of a MOSFET transistor,in accordance with an embodiment of the invention.

FIG. 4A depicts a top view of deposition of a dielectric layer and aninsulator layer, in accordance with an embodiment of the invention.

FIG. 4B depicts a section view of deposition of a dielectric layer andan insulator layer, in accordance with an embodiment of the invention.

FIG. 5A depicts a top view of a nano-channel formed in the insulatorlayer, in accordance with an embodiment of the invention.

FIG. 5B depicts a section view of a nano-channel formed in the insulatorlayer, in accordance with an embodiment of the invention.

FIG. 6A depicts a top view of formation of contacts for the source anddrain terminals of the current MOSFET transistor, in accordance with anembodiment of the invention.

FIG. 6B depicts a section view of formation of contacts for the sourceand drain terminals of the current MOSFET transistor, in accordance withan embodiment of the invention.

DETAILED DESCRIPTION

Embodiments of the present invention generally provide ametal-oxide-semiconductor field-effect transistor (MOSFET) device forsequencing deoxyribonucleic acid (DNA). A detailed description ofembodiments of the claimed structures and methods are included herein;however, it is to be understood that the disclosed embodiments aremerely illustrative of the claimed structures and methods that may beembodied in various forms. In addition, each of the examples given inconnection with the various embodiments is intended to be illustrative,and not restrictive. Further, the figures are not necessarily to scale,some features may be exaggerated to show details of particularcomponents. Therefore, specific structural and functional detailsdisclosed herein are not to be interpreted as limiting, but merely as arepresentative basis for teaching one skilled in the art to variouslyemploy the methods and structures of the present disclosure.

References in the specification to “one embodiment”, “an embodiment”,“an example embodiment”, etc., indicate that the embodiment describedmay include a particular feature, structure, or characteristic, butevery embodiment may not necessarily include the particular feature,structure, or characteristic. Moreover, such phrases are not necessarilyreferring to the same embodiment. Further, when a particular feature,structure, or characteristic is described in connection with anembodiment, it is submitted that it is within the knowledge of oneskilled in the art to affect such feature, structure, or characteristicin connection with other embodiments whether or not explicitlydescribed.

For purposes of the description hereinafter, the terms “upper”, “lower”,“right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, andderivatives thereof shall relate to the disclosed structures andmethods, as oriented in the drawing figures. The terms “overlying”,“atop”, “positioned on” or “positioned atop” mean that a first element,such as a first structure, is present on a second element, such as asecond structure, wherein intervening elements, such as an interfacestructure may be present between the first element and the secondelement. The term “direct contact” means that a first element, such as afirst structure, and a second element, such as a second structure, areconnected without any intermediary conducting, insulating orsemiconductor layers at the interface of the two elements.

The present invention will now be described in detail with reference tothe Figures. FIGS. 1A and 1B illustrate a top view and a section view ofa starting wafer including buried oxide layer 110 and semiconductorsubstrate 120, in accordance with one embodiment of the invention.Semiconductor substrate 120 is a substrate on which a MOSFET device forsequencing DNA may be formed. Semiconductor substrate 120 is asemiconductor material, preferably a silicon-containing materialincluding, but not limited to, silicon, germanium, silicon germaniumalloys, germanium alloys, indium alloys, carbon nanotube, graphene,silicon carbon alloys, or silicon germanium carbon alloys. Semiconductorsubstrate 120 is present above buried oxide layer 110. Buried oxidelayer 110 acts as an electrical insulator below semiconductor substrate120. In general, the thickness of semiconductor substrate 120 is between1 nm and 10 nm however, in embodiments of the invention where bulksilicon construction is used semiconductor substrate 120 may be thickerthan 10 nm. While the depicted embodiment includes an illustration ofsilicon on insulator (SOI) construction, it should be appreciated by oneskilled in the art that the invention is not limited to SOIconstruction, and that other types of semiconductor construction can beused in various embodiments of the invention, for example, bulk siliconconstruction. In embodiments where bulk silicon construction is used,buried oxide layer 110 may not be present in the starting wafer.

FIGS. 2A and 2B illustrate a top and section view of deposition andpatterning of hard mask layer 210. Hard mask layer 210 is used to definean area of semiconductor substrate 120 which is to be doped duringformation of source and drain terminals, as described in reference tothe following Figures. In a preferred embodiment, hard mask layer 210 issilicon nitride (SiN), deposited using, for example, low pressurechemical vapor deposition (LPCVD). Other materials with which hard masklayer 210 may be formed include, but are not limited to, hafnium oxide(Hf02) or titanium oxide. Hard mask layer 210 is of a sufficientthickness to protect portions of semiconductor substrate 120 from theaddition of dopants in later steps. In one embodiment, hard mask layer210 is between 10 nm and 50 nm thick and is preferably about 30 nmthick. A person of ordinary skill in the art would recognize thatchemical-mechanical planarization (CMP) steps may be inserted before andafter the deposition of hard mask layer 210 to ensure that the topsurfaces of both semiconductor substrate 120 and hard mask layer 210 arerelatively flat. The process of patterning hard mask layer 210 to definesource and drain terminals on semiconductor substrate 120 involves theuse of standard photolithographic processes to define the pattern ofsource and drain terminals in a layer of photoresist (not shown)deposited on hard mask layer 210. In various embodiments, standardphotolithographic processes are used to remove a portion of thephotoresist layer corresponding to the area of semiconductor substrate120 which is to be doped in later steps. The source and drain terminalpatterns defined in the photoresist layer are formed into hard masklayer 210 by removing hard mask layer 210 from the areas not protectedby the pattern in the photoresist layer. A portion of hard mask layer210 is removed using, for example, reactive ion etching (RIE). RIE useschemically reactive plasma, generated by an electromagnetic field, toremove various materials. A person of ordinary skill in the art willrecognize that the type of plasma used will depend on the material ofwhich hard mask layer 210 is composed, or that other etch processes,e.g., wet chemical etch, laser ablation, etc., may be used.

FIGS. 3A and 3B illustrate a top and section view of semiconductorsubstrate 120 with doped regions for the source and drain of the deviceand the removal of hard mask layer 210, in accordance with an embodimentof the invention. In the depicted embodiment, the portion ofsemiconductor substrate 120 to be doped is defined by the pattern inhard mask layer 210 and/or the layer of photoresist. In otherembodiments, a layer of photoresist alone is used to define the patternin semiconductor substrate 120 to be doped, and hard mask layer 210 isnot included in such embodiments. The type of dopant is selected basedon the type of MOSFET which is to be created. For example, an nFET typeof transistor is doped with an n-type material such as phosphorus.Similarly, a pFET type of transistor is doped with a p-type materialsuch as boron. In general, hard mask layer 210 is used to protect theareas of semiconductor substrate 120 which are not to be doped while theportions of semiconductor substrate 120 which are not protected by hardmask layer 210 are doped.

In various embodiments, the source and drain terminals are constructedsuch that the separation between a source terminal and its respectivedrain terminal is between 1 nm and 6 nm. In the depicted embodiment ofthe invention the separation between the source and drain terminals ofthe device is between 1 nm and 2 nm. Additionally, in some embodiments,multiple transistors may be present along nano-channel 500 for thepurpose of re-reading a portion of the same strand of DNA in order tofacilitate noise reduction, error correction, or any other processintended to increase the accuracy or speed of reading a sequence of DNAbase pairs, by including the use of multiple transistors. Theseembodiments may include additional data processing components or the useof software elements not included in the depicted embodiment.

Remaining portions of hard mask layer 210 are removed once the sourceand drain terminals have been formed in semiconductor substrate 120through the process of doping semiconductor substrate 210. Hard masklayer 210 is removed using, for example, RIE. RIE uses chemicallyreactive plasma, generated by an electromagnetic field, to removevarious materials. A person of ordinary skill in the art will recognizethat the type of plasma used will depend on the material of which hardmask layer 210 is composed, or that other etch processes, e.g., wetchemical etch, laser ablation, etc., may be used.

FIGS. 4A and 4B illustrate top and section views of the deposition ofdielectric layer 410 and insulator 420, in accordance with an embodimentof the invention. In a preferred embodiment, dielectric layer 410 is ahigh-k dielectric such as Hafnium oxide. In general, the purpose ofdielectric layer 410 is to prevent electrical conduction between astrand of DNA and the source and drain terminals present insemiconductor substrate 120. Electric fields created by the charge andpolarization of individual nucleotides within the strand of DNA are ableto pass through dielectric layer 410, however the material of whichdielectric layer 410 is composed must not be conductive in order for thedevice to function correctly. Insulator 420 is deposited on dielectriclayer 410 and can be composed of Si02, SiJN4 or other dielectricmaterials. It should be appreciated by one skilled in the art thatadditional CMP steps may be present before and after the deposition ofboth dielectric layer 410 and insulator 420. In some embodiments,dielectric layer 410 is formed by oxidizing the top portion ofsemiconductor substrate 120 using a process such as plasma oxidation,plasma nitridation, thermal oxidation, etc.

FIGS. 5A and 5B depict top and section views of formation ofnano-channel 500, according to an embodiment of the invention.Nano-channel 500 is created by etching a portion of insulator 420 using,for example, wet chemical etching or dry etching. In one embodiment,standard photolithographic processes are used to define the pattern ofnano-channel 500 in a layer of photoresist (not shown) deposited oninsulator 420. The nano-channel pattern may then be formed in insulator420 by removing insulator 420 from the areas not protected by thepattern in the photoresist layer. Insulator 420 is removed using, forexample, RIE. A person of ordinary skill in the art will recognize thatthe type of plasma used will depend on the material of which insulator420 is composed, or that other etch processes, e.g., wet chemical etch,laser ablation, etc., may be used. It should also be appreciated thatthe process used to etch the desired portion of insulator 420 must beselected such that the process does not remove any portion of dielectriclayer 410, as the presence of dielectric layer 410 is required for theoperation of the device. In general, nano-channel 500 is formed byremoving a portion of insulator 420 in order to facilitate the movementand positioning of a strand of DNA over the source and drain terminalsformed in semiconductor substrate 120. In various embodiments,nano-channel 500 has a width of between 5 nm and 100 nm, however inpreferred embodiments nano-channel 500 has a width of roughly 10 nm. Inthe depicted embodiment, the removed portion of insulator layer 420gradually narrows to form nano-channel 500. This narrowing portion maynot be present in other embodiments of the invention, and additionalelements may be added to ensure that strands of DNA are able to enterthe nano-channel in such embodiments.

In general, the purpose of nano-channel 500 is to guide the movement ofa strand of DNA such that the strand of DNA passes directly over thesource and drain terminals formed in semiconductor substrate 120.Situations where self-avoiding polymers such as DNA are enclosed in verynarrow environments (such that the width of the environment is less thanthe radius of gyration of the polymer), such as nano-channel 500,prevent the polymer from folding back on itself, and yield a uniformdistribution of monomers (such as DNA nucleotides) throughout the lengthof the polymer, which provide an ideal environment for sequencingportions of DNA.

A given nucleotide or group of nucleotides present between the sourceand drain terminals of the device acts as the gate terminal in thecurrent MOSFET device. A field-effect resulting from the charge orpolarity of the given nucleotide or combination of nucleotides isidentified based on the amount of current between the source and drainterminals of the device. The amount of current present is the result ofthe change in conductivity of the portion of semiconductor substrate 120between the source and drain terminals due to the field effect generatedby the nucleotide or group of nucleotides present in the active area. Itshould be appreciated that the number of consecutive nucleotidescontributing to the overall field-effect measured by the device isdetermined by the separation between the source and drain terminals. Inthe depicted embodiment, the separation between the source and drainterminals is 6 nm. On average, the separation between consecutivenucleotides in a strand of DNA is measured to be 0.34 nm. Based on thisinformation, a transistor with a source-drain separation of 6 nm wouldfacilitate sequencing 18 nucleotides at a time. Similarly, in apreferred embodiment, a transistor with a source-drain separation of 1nm would facilitate scanning only three nucleotides at a time. Ingeneral, a smaller source-drain separation is preferred because thefield-effect generated by a single nucleotide is more identifiable whenfewer nucleotides are present in the active area.

Before a strand of DNA can be read, a voltage source is used to apply avoltage between the source and drain terminals of the device. In variousembodiments the voltage applied between the source and drain terminalsof the device depends on the separation between the source and drainterminals. In general, the voltage source is capable of applying aconstant voltage and measuring any current flow between the source anddrain terminals of the device which result from a field effect generatedby a nucleotide or group of nucleotides currently present in the activearea. In some embodiments, the voltage source is a device connected to acomputer or another electronic device capable of storing and analyzinginformation related to the change in the current flow between the sourceand drain terminals over time. The process of sequencing DNA involvesrecording the change in current flowing between the source terminal andthe drain terminal of the device in order to determine the field-effectgenerated by the charge and polarity of the portion of nucleotidescurrently being sequenced. As a strand of DNA moves through thenano-channel, nucleotides continuously pass through the active areabetween the source and drain terminals where the field effect ismeasured. In some embodiments, before the sequencing of an unknownportion of DNA begins, the device is calibrated by using a strand of DNAcontaining a known sequence of nucleotides to determine the expectedfield-effects for various combinations of nucleotides. In theseembodiments, data collected during calibration is recorded in a tablelisting the expected field-effect for each possible combination ofnucleotides. For example, in an embodiment where four nucleotides areread at a time, there are 256 (4⁴) possible combinations of nucleotideswhich can be present in the active area at any given time. Identifyingthe specific combination of nucleotides currently present andcontributing to the field-effect is performed by measuring the currentpresent between the source and drain terminals and comparing this valueto the current expected for various known combinations of nucleotides.

In embodiments where the separation between the source and drainterminals is larger, more nucleotides may be able to fit between thesource and drain terminals. The increase in the number of nucleotideswhich can fit between the source and drain terminals can cause anexponential increase in the number of possible combinations ofnucleotide sequences which much be chosen from in order to determine thecurrent sequence of nucleotides present between the source and drainterminals.

One such example would be the case of a 10 nm separation between thesource and drain terminals, which can allow roughly 30 nucleotides to bepresent in the active area. With 30 nucleotides present in the activearea, and four possible bases that each nucleotide can contain (adenine(A), thymine (T), guanine (G), cytosine(C)), the total number ofpossible combinations (4³⁰) is extremely large. In these embodiments itis much more desirable to examine only the changes in the currentbetween the source and the drain to determine which specific nucleotidesare entering and leaving the active area to cause the change in thefield-effect. For example, in an embodiment where the active area issufficiently wide to accommodate 4 nucleotides, the current set ofnucleotides present in the active area is determined to be GTAC. As thestrand of DNA moves across the active area, the set of nucleotideschanges to CTAC, and from this information it can be determined that theG nucleotide present in the initial set of nucleotides has left theactive area and been replaced by a C nucleotide. As the strand of DNAcontinues to pass along the active area, the order in which newnucleotides arrive to the active area can be used to determine the orderin which nucleotides are present along the strand of DNA. Thisinformation can be verified by observing the order in which the samenucleotides leave the active area, or arrive at a second active areapresent along nano-channel 500.

In the depicted embodiment, insulator 420 is etched to form nano-channel500 which is used to position a portion of DNA directly above the sourceand drain terminals (see FIG. 3). In some embodiments, a nano-tunnel maybe formed by adding a planar portion of insulating material above thenano-channel to form a portion of material present above nano-channel500. In other embodiments, a nano-tunnel is formed by horizontallyetching a portion of insulator 420 and preserving the topmost portion ofinsulator 420 to form a nano-tunnel with a portion of insulator 420present above the nano-tunnel.

FIGS. 6A and 6B depict top and section views of formation of metalcontacts 610, 620, 630, and 640. Metal contacts 610, 620, 630, and 640are used for connecting the current MOSFET device to other electricalcomponents such as a computer or other device for processing andinterpreting the signal transmitted from the current MOSFET device. Aperson of ordinary skill in the art will recognize that the formation ofcontacts 610, 620, 630, and 640 includes the steps of etching a portionof insulator 420, dielectric layer 410, and semiconductor substrate 120and depositing a contact material into the etched portion of the layer.A contact material can comprise a metal such as tungsten, titanium,titanium nitride, or copper, and may be deposited by a process such aschemical vapor deposition (CVD). After the contact metal used to formcontacts 610, 620, 630, and 640 is deposited, CMP may be used to removeexcess contact material present above the top of insulator 420.

It should be appreciated that although the depicted embodimentillustrates the formation of four metal contacts, other embodiments mayinclude the formation of two, four, six, eight, or any even number ofmetal contacts. In general, two metal contacts are formed for eachtransistor present along nano-channel 500. In the depicted embodiment,the two transistors present along nano-channel 500 require the formationof four metal contacts. In the depicted embodiment, contacts 610 and 630connect the source terminals of the first and second transistors presentalong nano-channel 500 to outside electrical components respectively.Similarly, contacts 620 and 640 connect the drain terminals of the firstand second transistors present along nano-channel 500 to outsideelectrical components respectively.

The method as described above is used in the fabrication of integratedcircuit chips.

The resulting semiconductor device may be included on a semiconductorsubstrate consisting of many devices and one or more wiring levels toform an integrated circuit chip. The resulting integrated circuitchip(s) can be distributed by the fabricator in raw wafer form (that is,as a single wafer that has multiple unpackaged chips), as a bare die, orin a packaged form. In the latter case the chip is mounted in a singlechip package (such as a plastic carrier, with leads that are affixed toa motherboard or other higher level carrier) or in a multichip package(such as a ceramic carrier that has either or both surfaceinterconnections or buried interconnections). In any case, the chip isthen integrated with other chips, discrete circuit elements, and/orother signal processing devices as part of either (a) an intermediateproduct, such as a motherboard, or (b) an end product. The end productcan be any product that includes integrated circuit chips, ranging fromtoys and other low-end applications to advanced computer products havinga display, a keyboard or other input device, and a central processor.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, elements,components, and/or groups thereof.

Having described preferred embodiments of a MOSFET device for sequencingDNA (which are intended to be illustrative and not limiting), it isnoted that modifications and variations may be made by persons skilledin the art in light of the above teachings. It is therefore to beunderstood that changes may be made in the particular embodimentsdisclosed which are within the scope of the invention as outlined by theappended claims.

What is claimed is:
 1. A method comprising: providing a sensorcomprising: a buried oxide layer; a substrate layer formed on and abovethe buried oxide layer; a first source region formed in a first portionof the substrate layer and a first drain region formed in a secondportion of the substrate layer, the first source region and the firstdrain region spaced a first distance apart; a dielectric layer formed onthe substrate layer; an insulative layer formed on the dielectric layer;a nano-channel formed in the insulative layer, wherein the nano-channelpasses over the first source region and the first drain region such thateach of the first source region and the first drain region are onlybelow a bottom side of the nano-channel; and a contact for each sourceand drain region; connecting a voltage source across the first sourceregion and the first drain region; and measuring, by one or moreprocessors, a first current flow between the first source region and thefirst drain region.
 2. The method of claim 1, wherein the first end ofthe nano-channel has a first width that gradually decreases to a secondwidth along the nano-channel.
 3. The method of claim 1, wherein thesensor further comprises: a second source region formed in a thirdportion of the substrate layer and a second drain region formed in afourth portion of the substrate layer, the second source region and thesecond drain region spaced a second distance apart.
 4. The method ofclaim 1, further comprising: measuring, by one or more processors, asecond current flow between the first source region and the first drainregion when a portion of a strand of DNA is present in the nano-channelbetween the first source region and the first drain region.
 5. Themethod of claim 4, further comprising: determining, by one or moreprocessors, a first set of one or more DNA nucleotides corresponding tothe first current flow; determining, by one or more processors, a secondset of one or more DNA nucleotides corresponding to the second currentflow; and identifying, by one or more processors, at least one differentDNA nucleotide present within the first set of one or more DNAnucleotides and the second set of one or more DNA nucleotides.
 6. Themethod of claim 4, further comprising: calculating, by one or moreprocessors, a difference between the measured first current flow and themeasured second current flow; and identifying, by one or moreprocessors, a change in presence of one or more DNA nucleotides betweena first portion of the strand of DNA and the second portion of thestrand of DNA based on the calculated difference.
 7. The method of claim1, wherein the sensor further comprises: a second source region and asecond drain region formed in the substrate layer, the second sourceregion and the second drain region spaced a second distance apart. 8.The method of claim 7, further comprising: connecting a voltage sourceacross the second source region and the second drain region, the voltagesource capable of measuring current flow through the second sourceregion and the second drain region when at least one DNA nucleotide ispresent in the nano-channel between the second source region and thesecond drain region; measuring, by one or more processors, a thirdcurrent flow between the second source region and the second drainregion, wherein a first portion of the strand of DNA is present in thenano-channel between the second source region and the second drainregion; comparing, by one or more processors, the measured first currentflow and the measured third current flow; and verifying, by one or moreprocessors, whether the measured first current flow and the measuredthird current flow are equal to within a predetermined threshold.
 9. Themethod of claim 6, wherein the first distance and the second distanceare equal.
 10. The method of claim 6, wherein the first distance is of adifferent length than the second distance.
 11. The method of claim 1,wherein the first distance is less than or equal to 6 nanometers.